Epicutaneous sensitization results in IgE-dependent intestinal mast cell expansion and food-induced anaphylaxis - 30/01/13
, Michael F. Gurish, PhD b, , Oliver T. Burton, PhD a, Sabine Leisten, MS a, Erin Janssen, MD, PhD a, Hans C. Oettgen, MD, PhD a, Jacqueline Beaupré, BA a, Christopher N. Lewis, BA a, K. Frank Austen, MD b, Stephanie Schulte, MD c, Jason L. Hornick, MD, PhD c, Raif S. Geha, MD a, ⁎ 
, Michiko K. Oyoshi, PhD a, ⁎ Corresponding author: Michiko K. Oyoshi, PhD or Raif S. Geha, MD, Karp 10, Division of Immunology, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115.Abstract |
Background |
Sensitization to food antigen can occur through cutaneous exposure.
Objective |
We sought to test the hypothesis that epicutaneous sensitization with food antigen predisposes to IgE-mediated anaphylaxis on oral allergen challenge.
Methods |
BALB/c mice were epicutaneously sensitized by repeated application of ovalbumin (OVA) to tape-stripped skin over 7 weeks or orally immunized with OVA and cholera toxin (CT) weekly for 8 weeks and then orally challenged with OVA. Body temperature was monitored, and serum mouse mast cell protease 1 levels were determined after challenge. Tissue mast cell (MC) counts were examined by using chloroacetate esterase staining. Levels of serum OVA-specific IgE and IgG1 antibodies and cytokines in supernatants of OVA-stimulated splenocytes were measured by means of ELISA. Serum IL-4 levels were measured by using an in vivo cytokine capture assay.
Results |
Epicutaneously sensitized mice exhibited expansion of connective tissue MCs in the jejunum, increased serum IL-4 levels, and systemic anaphylaxis after oral challenge, as evidenced by decreased body temperature and increased serum mouse mast cell protease 1 levels. Intestinal MC expansion and anaphylaxis were IgE dependent because they did not occur in epicutaneously sensitized IgE−/− mice. Mice orally immunized with OVA plus CT did not have increased serum IL-4 levels, expanded intestinal MCs, or anaphylaxis after oral challenge, despite OVA-specific IgE levels and splenocyte cytokine production in response to OVA stimulation, which were comparable with those of epicutaneously sensitized mice.
Conclusion |
Epicutaneously sensitized mice, but not mice orally immunized with antigen plus CT, have expansion of intestinal MCs and IgE-mediated anaphylaxis after single oral antigen challenge. IgE is necessary but not sufficient for food anaphylaxis, and MC expansion in the gut can play an important role in the development of anaphylaxis.
Le texte complet de cet article est disponible en PDF.Key words : Food allergy, epicutaneous sensitization, IgE, mast cells, anaphylaxis
Abbreviations used : AD, CAE, CT, CTMC, IL-4R, MC, MLN, mMCP-1, OVA, Treg, WT
Plan
| Supported by National Institutes of Health (NIH) grants AR-047417 and R01-AI083516. L.M.B. was supported by training grant T32-AI-007512 and the 2010 American Academy of Allergy, Asthma & Immunology/Food Allergy Initiative Howard Gittis Memorial Third/Fourth Year Fellowship/Junior Faculty Research Award. M.K.O. was supported by the Harvard Digestive Disease Center, NIH grant P30 DK34845, and the Boston Children’s Hospital Faculty Career Development Fellowship/Eleanor and Miles Shore Program for Scholars in Medicine at Harvard Medical School. M.F.G. was supported by National Institute of Allergy and Infectious Diseases (NIAID) grant RO1-AI083516. H.C.O. was supported by NIH/NIAID grant R56 AI100889-01 and US Environmental Protection Agency grant 83482501. |
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| Disclosure of potential conflict of interest: S. Leisten has received research support from the German Academic Exchange Service (DAAD). R. S. Geha has received research support from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 2
P. 451 - février 2013 Retour au numéro
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